Although the incidence of esophageal adenocarcinoma is rising more rapidly than that of any other malignancy, little is known about its pathogenesis. In particular, little population-based information is known about its main precursor lesion, Barrett's esophagus. The presence of Barrett's esophagus, a metaplastic esophageal columnar epithelium, effectively identifies persons at risk for esophageal adenocarcinoma. Thus, there is a compelling rationale for characterizing the incidence and major modifiable risk factors for Barrett's esophagus, and how these relate to purported risk factors for esophageal adenocarcinoma. Specific Aims/Methods: A. Evaluate the association between obesity/body fat distribution and Barrett's esophagus using a nested case-control study in the Northern California Kaiser Permanente (NCKP) population. The NCKP population contains approximately 3 million people, and is representative of the gender and ethnic distribution of Northern California. The study would use 313 cases, 313 population-based controls, and 313 controls with gastroesophageal reflux disease (who do not have Barrett's esophagus). We would employ a supplementary dietary questionnaire to evaluate for potential dietary confounders of the obesity-Barrett's esophagus relationship. B. Evaluate the association between serum antibody status for Helicobacter Pylori (including the virulent cagA+ strain) and Barrett's esophagus using a case-control study. C. Assay Barrett's esophagus patients and controls for iron stores and heterozygosity for the C282Y hemochromatosis gene mutation. D. Use the patients identified in these case-control studies to estimate the annual population-based incidence of Barrett's esophagus diagnosis. Obesity and body fat distribution, H.pylori infection, and iron stores represent potentially major, modifiable risk factors for Barrett's esophagus and esophageal adenocarcinoma. Our proposed study will: substantially extend current knowledge regarding the epidemiology of Barrett's esophagus; may partially explain why Barrett's esophagus/esophageal adenocarcinoma occurs predominantly in Caucasian males; estimate the population-based incidence of Barrett's esophagus diagnosis in the United States; and provide information for future intervention trials.